NK cells: use and functionality

Towards allogeneic "off-the-shelf" cell products

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NK cells play an important role in control and even cure of haematological malignancies. Due to their tightly regulated “natural killing" and antibody dependent cellular cytotoxicity (ADCC), NK cells have the capability to control viral infections, target cancer and kill senescent cells. Further insight in NK cell receptor biology as well as possibilities to exploit NK cells for adoptive immunotherapy will fuel translational research to bring NK cell based therapy to clinical trials in a broad range of diseases. In allogeneic stem cell transplantation (SCT), NK cells have shown to mediate graft-versus-leukaemia (GVL) immunity towards recipient tumour cells without attacking normal tissues leading to graft-versus-host disease (GVHD). The separation between GVL and GVHD might be explained by reduced (HLA-matched SCT) or presence of non-self (HLA-mismatched SCT) antigen expression on leukaemic cells of the patient combined with selective up regulation of activating ligands. This makes NK cell based immunotherapy an attractive adjuvant therapy for acute myeloid leukaemia and other malignancies.

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In order to use these cells as immunotherapeutic tool Glycostem was able to circumvent a number of existing problems and developed a novel technique to generate large amounts of highly functional NK cells for clinical use. The first aim of Glycostem's strategy has been the clinical application of oNKord® in a phase I/II clinical trial, to document the safety and toxicity of the current product candidate. Glycostem and its collaborating partner Radboud UMC (Nijmegen, the Netherlands) are conducting a phase I/II clinical trial in poor risk AML patients.

The future challenge will be to bring NK cell adoptive therapy a step further from personalized medicine towards more generic medication. Lessons learned from haploidentical NK cell infusion trials in the past clearly suggest that NK cell products for future immunotherapy trials should be improved in cell numbers, activity, availability and be devoid of contaminating cells like T or B cells. The main focus of Glycostem is to use the novel production method for the production of NK cell immunotherapy products, but additionally to study NK cell development, biology and function.